Genetically Modified Lactococcus lactis for Delivery of Human Interleukin-10 to Dendritic Cells

Interleukin-10 (IL-10) plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs) to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L.  lactisIL-10) on DC function in vitro. Monocyte-derived DC incubated with L.  lactis...

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Bibliographic Details
Main Authors: Inge L. Huibregtse, Sebatian A. Zaat, Martien L. Kapsenberg, Maria A. Sartori da Silva, Maikel P. Peppelenbosch, Sander J. H. van Deventer, Henri Braat
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2012/639291
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Summary:Interleukin-10 (IL-10) plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs) to induce suppressor Th-cells. We have tested the modulating effect of L. lactis secreting human IL-10 (L.  lactisIL-10) on DC function in vitro. Monocyte-derived DC incubated with L.  lactisIL-10 induced effector Th-cells that markedly suppressed the proliferation of allogenic Th-cells as compared to L. lactis. This suppressive effect was only seen when DC showed increased CD83 and CD86 expression. Furthermore, enhanced production of IL-10 was measured in both L.  lactisIL-10-derived DC and Th-cells compared to L. lactis-derived DC and Th-cells. Neutralizing IL-10 during DC-Th-cell interaction and coculturing L.  lactisIL-10-derived suppressor Th-cells with allogenic Th-cells in a transwell system prevented the induction of suppressor Th-cells. Only 130 pg/mL of bacterial-derived IL-10 and 40 times more exogenously added recombinant human IL-10 were needed during DC priming for the generation of suppressor Th-cells. The spatially restricted delivery of IL-10 by food-grade bacteria is a promising strategy to induce suppressor Th-cells in vivo and to treat inflammatory diseases.
ISSN:1687-6121
1687-630X